Corticosteroid Suppresses VEGF in Infantile Hemangioma
Study of dexamethasone treatment in mouse model sheds light on mechanism of action
WEDNESDAY, March 17 (HealthDay News) -- In a mouse model of infantile hemangioma, injections of the corticosteroid dexamethasone were able to suppress vasculogenesis by inhibiting the expression of vascular endothelial growth factor A (VEGF-A), according to a study in the March 18 issue of the New England Journal of Medicine.
Shoshana Greenberger, M.D., of Children's Hospital Boston, and colleagues implanted hemangioma-derived human stem cells and endothelial cells isolated from human umbilical-cord blood into immune-deficient mice. The researchers treated the mice with injections of the corticosteroid dexamethasone daily for a week, while a control group received saline injections. To rule out metabolic effects from the mouse host, the researchers also treated the cell types with dexamethasone in vitro for three days before injecting them into other mice.
The mice that had the dexamethasone injections after implantation and the mice that received the hemangioma-derived stem cells treated before implantation exhibited inhibited tumor vasculogenesis resulting from VEGF-A suppression, the researchers found. However, pretreatment of the hemangioma-derived endothelial cells or umbilical-vein endothelial cells did not suppress VEGF-A. Dexamethasone treatment also suppressed several other proangiogenic factors, including interleukin-6, urokinase plasminogen activator receptor, monocyte chemoattractant protein 1, and matrix metalloproteinase 1.
"In a murine model, dexamethasone inhibited the vasculogenic potential of stem cells derived from human infantile hemangioma. The corticosteroid also inhibited the expression of VEGF-A by hemangioma-derived stem cells, and silencing of VEGF-A expression in these cells inhibited vasculogenesis in vivo," the authors write.